Autoimmune disease is caused when one's own immune system incorrectly attacks one's own tissue. It is known to treat patients suffering from autoimmune disorders by intravenously introducing immunoglobulin into the patients. A period of remission in the disease can be produced by this treatment. Although the use of immunoglobulin has been relatively effective in the treatment of autoimmune disorders, the mechanism of action is unknown. The intravenous administration of immunoglobulin (IVIG) to any particular patient may cause side effects, such as fever and muscle aches, headaches, nausea and vomiting, dizziness, and tachycardia. There is also the potential of transferring to the patient disease from the person who donated blood used for the manufacture of this immunoglobulin. At a cost of approximately $100/gram, treatment with immunoglobulin is also relatively expensive, amounting to many thousands of dollars for each treatment. There has recently been a shortage in the availability of IVIG.
Standardized parenteral nutritional protocols, which include a combination of amino acids, have been traditionally given to nourish patients who could not be fed orally or gastrically. In one such case, I had used a standardized parenteral nutritional protocol to nourish a patient who had been suffering from an autoimmune disease. The patient, a 70-year old female weighing approximately 40 kg, presented herself to me in 1990 with generalized weakness and ptosis (drooping of the eyelids). The diagnosis of Myasthenia Gravis without Thymoma, an autoimmune disorder, was made following a Tensilon test of the thenar muscle and elevated Acetylcholine receptor antibody titer measured in the blood. The Acetylcholine receptor antibody causes muscle weakness by attacking the muscle endplate, thus interfering with the Acetylcholine synapse between the nerve and the muscle.
The patient regained good strength on a combination of Pyridostigmine and Prednisone, drugs which have been traditionally used to treat the symptoms of Myasthenia Gravis by respectively making more acetylcholine available at the muscle endplate and by reducing the inflammatory response at the muscle end plate plus reducing the amount of antibody formation. The daily administration of Pyridostigmine and Prednisone were continued in order to maintain reasonable control of the symptoms of the disease.
On Nov. 6, 1992, the patient underwent a bowel operation for the correction of an enterorectal fistula. On Nov. 8, 1992, because of her inability to be orally or gastrically fed, the patient was intravenously administered a standardized parenteral nutritional protocol, which was continued for six days until she was discharged from the hospital on Nov. 14, 1992. No change in the patient's Myasthenia Gravis status was noted at this time. As the patient was able to be orally fed, she was not administered the standardized parenteral nutritional protocol after discharge from the hospital. To maintain control of the effects of the Myasthenia Gravis, the patient was continued on Pyridostigmine and Prednisone.
On Nov. 26, 1992, the patient suffered from abdominal discomfort and tenderness and was readmitted to the hospital. Oral feeding ceased, and on Nov. 27, 1992 (Day 1 of the intravenous feeding), I again administered the standardized parenteral nutritional protocol (First Protocol) to the patient at a rate of 100 cc. per hour. The composition of this protocol with the appropriate quantities of each element is set forth in Table 1.
TABLE 1 ______________________________________ Individual Elements and the Quantity of each Element in 100 cc of a First Standardized Parenteral Nutritional Protocol Elements Amount ______________________________________ Distilled Water Essential Amino Acids Isoleucine USP 0.21 gms Leucine USP 0.27 gms Lysine as Lysine acetate USP 0.31 gms Methionine USP 0.16 gms Phenylalanine USP 0.17 gms Threonine USP 0.12 gms Tryptophan USP 0.046 gms Valine USP 0.2 gms Non-Essential Amino Acids Alanine USP 0.21 gms Arginine USP 0.29 gms Histidine USP 0.085 gms Proline USP 0.34 gms Serine USP 0.18 gms Glycine USP 0.42 gms Cystein USP 0.014 gms Lipids 10 gms Soybean Oil * Egg Phosphatides * Electrolytes Sodium Chloride 80 mEq/liter Sodium Phosphate 25 mEq/liter Potassium Chloride 30 mEq/liter Calcium Gluconate 12 mEq/liter Magnesium Sulfate 8 mEq/liter Zinc Sulfate 20 mg/liter Trace Elements Zinc 5 mg Copper 2 mg Manganese 0.5 mg Chromium 10 mcg Selenium 60 mcg Daily Vitamins Ascorbic Acid 500 mg Vitamin A 1000 i.u. Vitamin D 1000 i.u. Thiamine 50 mg Riboflavin 10 mg Pyridoxine 5 mg Niacin 100 mg Vitamin E 5 i.u. Dexpanthenol 25 mg Vitamin K 10 mg ______________________________________
On Day 3 of the intravenous feeding, the patient felt much stronger and continued to feel strong for several days thereafter despite having an elevated Acetylcholine receptor antibody titer of 25, with less than 0.5 being normal.
On Day 5 of the intravenous feeding, the patient developed a cholinergic attack secondary to the Pyridostigmine that was continuously administered to her. This resulted in abdominal cramping. The cholinergic attack was relieved by the intravenous administration of Atropine, which countered the effect of Pyridostigmine. The administration of the Pyridostigmine and Prednisone to the patient was discontinued.
On Day 6 of the intravenous feeding, the patient felt strong, despite the discontinuation of the Pyridostigmine and Prednisone.
On Day 7 of the intravenous feeding, the patient continued to get stronger despite the fact that her Acetylcholine receptor antibody titer had risen to 30, a level that typically results in weakness. This indicated to me that the Myasthenia Gravis was not being controlled by the reduction of the Acetylcholine receptor antibody titer, a result typically achieved by the administration of Prednisone, but rather by blocking the effects of the Acetylcholine receptor antibody. Since the administration of the Pyridostigmine had been discontinued, this indicated to me that the effect of the high Acetylcholine receptor antibody titer on the muscle endplates was being countered by the intravenous administration of the First Protocol.
The patient was discharged from the hospital on Dec. 14, 1992, after which she was continued on the First Protocol until Mar. 23, 1993. During this period, the patient's Acetylcholine receptor antibody titer had been measured at 57, 38, and 30 on the respective dates of Jan. 4, 1993, Jan. 25, 1993 and Feb. 18, 1993.
The patient's Myasthenia Gravis continued in remission until Mar. 31, 1993, eight days after the intravenous feeding was discontinued. Two days later, on Apr. 2, 1993, the patient was continued on Pyridostigmine 30 mg twice a day and the patient regained her strength. Although the effects of Myasthenia Gravis typically had to be controlled by a combination of Pyridostigmine and Prednisone, the patient's Myasthenia Gravis continued in partial remission for over 5 months necessitating the use of only Pyridostigmine without the administration of Prednisone. This indicated to me that the intravenous administration of the First Protocol had a prolonged positive effect in treating the Myasthenia Gravis.
On Sep. 13, 1993, the patient had increased weakness and was administered Prednisone 40 mg daily, in addition to the Pyridostigmine. A week later the Prednisone was reduced to 20 mg every other day. The patient was continued on this combination of Pyridostigmine and Prednisone, a treatment that was similar to that given to her prior to the bowel operation. The patient's Acetylcholine receptor antibody titer was measured at 28.7 on Aug. 11, 1993, and at 14 on Oct. 23, 1993, at which time the patient had been continuously administered Prednisone. The patient remained strong until February 1997.